This invention is related to solid state sensors and, more particularly, to the use and preparation of a porous semiconductor such as a silicon wafer for the quantitative and qualitative analysis of an analyte such as an organic analyte.
Solid-state sensors and particularly biosensors have received considerable attention lately due to their increasing utility in chemical, biological, and pharmaceutical research as well as disease diagnostics. In general, biosensors consist of two components: a highly specific recognition element and a transducing structure that converts the molecular recognition event into a quantifiable signal. Biosensors have been developed to detect a variety of biomolecular complexes including oligonucleotide pairs, antibody-antigen, hormone-receptor, enzyme-substrate and lectin-glycoprotein interactions. Signal transductions are generally accomplished with electrochemical, field-effect transistor, optical absorption, fluorescence or interferometric devices.
It is known that the intensity of the visible photoluminescence changes of a porous silicon film depend on the types of gases adsorbed to its surface. Based on this phenomenon, a simple and inexpensive chemical sensor device was developed and disclosed in U.S. Pat. No. 5,338,415.
As disclosed in that patent, porous films of porous films of silicon (Si) can be fabricated that display well-resolved Fabry-Perot fringes in their optical reflectance properties. The production of a porous silicon (Si) layer that is optically uniform enough to exhibit these properties may be important for the design of etalons (thin film optical interference devices for laser spectroscopy applications) and other optical components utilizing porous Si wafers. Such interference-based spectra are sensitive to gases or liquids adsorbed to the inner surfaces of the porous Si layer.
Ever increasing attention is being paid to detection and analysis of low concentrations of analytes in various biologic and organic environments. Qualitative analysis of such analytes is generally limited to the higher concentration levels, whereas quantitative analysis usually requires labeling with a radioisotope or fluorescent reagent. Such procedures are time consuming and inconvenient. Thus, it would be extremely beneficial to have a quick and simple means of qualitatively and quantitatively detect analytes at low concentration levels. The invention described hereinafter provides one such means.
The subject invention contemplates the detection and, if desired, measurement of the wavelength shifts in the reflectometric interference spectra of a porous semiconductor substrate such as a silicon substrate that make possible the highly sensitive detection, identification and quantification of small molecules and particularly, small organic molecules (i.e., carbon-containing molecules e.g., biotin, and the steroid digoxigenin), short DNA oligonucleotides (e.g., 16-mers), and proteins (e.g., streptavidin and antibodies). The binding of inorganic species such as metal ions is also contemplated. Most notably, the sensor of the subject invention has been shown to be highly effective in detecting multiple layers of biomolecular interactions, termed xe2x80x9ccascade sensingxe2x80x9d, including sensitive detection of small molecule recognition events that take place relatively far from the silicon surface.
In an exemplary embodiment, a p-type silicon (Si) wafer (substrate) is galvanostatically etched in a hydrofluoric acid (HF)-containing solution. The etched wafer is rinsed with ethanol and dried under a stream of nitrogen gas. Reflection of white light off the porous silicon results in an interference pattern that is related to the effective optical thickness. The binding of an analyte to a recognition partner immobilized in the porous silicon substrate results in a change in the refractive index, which is detected as a wavelength shift in the reflection interference pattern.
One benefit of the present invention is the provision of a device for detecting the presence of target (analyte) molecules such as biological or organic compound molecules at very low concentrations.
An advantage of the present invention is the provision of a means for detecting the presence of multilayered molecular assemblies.
Still another benefit of the present invention is a device that is capable of quantitatively detecting an analyte.
Still another advantage of the present invention is that the presence of an analyte in a sample solution can often be detected by visual inspection, and without the need for special apparatus.
Still further benefits and advantages will be apparent to a worker of ordinary skill from the disclosure that follows.